TY - JOUR

T1 - Sex dimorphism in the Fgf21 gene expression in liver and adipose tissues is dependent on the metabolic condition

AU - Bazhan, Nadezhda

AU - Jakovleva, Tatiana

AU - Balyibina, Natalia

AU - Dubinina, Anastasia

AU - Denisova, Elena

AU - Feofanova, Natalia

AU - Makarova, Elena

N1 - Publisher Copyright: © 2019 Evgeniya A. Karpova, Alexandra Yu. Nabieva, Tatiana D. Fershalova, Yuliya L. Yakimova, Nataliya V. Tsybulya.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Fibroblast growth factor-21 (FGF21) beneficially affects carbohydrate and lipid metabolism. Previously, a sex-specific activation of Fgf21 expression was observed in humans and animals with metabolic diseases. It is unknown whether the sex differences in the Fgf21 expression are manifested in response to the natural physiological situations of fasting and refeeding. The aim of this work was to determine liver, White Adipose Tissue (WAT) and Brown Adipose Tissue (BAT) expression of genes related to FGF21 signaling in response to 24 h fasting, 6 h refeeding (after 24 h fasting) and Diet-Induced Obesity (DIO) in C57Bl mice of both sexes. Obesity was induced by the consumption of palatable food for 10 weeks. mRNA levels of peroxisome proliferator-activated receptor-a and -γ (Pparα, Pparγ), FGF21 (Fgf21), coactivator of FGF receptors (Klb) and transcriptional coactivator (Pgc-1α) were measured by RT-PCR. The study showed that the fasting-induced increases in hepatic Fgf21 gene expression and circulating FGF21 levels, as well as refeeding-induced increases in local WAT and BAT Fgf21 gene expression, were biased toward females. DIO-induced increase in circulating FGF21 levels, as well as in Fgf21 gene expression in the liver and BAT, were biased toward males. Considering that FGF21 is a novel metabolic regulator of energy homeostasis, sex differences in the responses to anabolic and catabolic stimulus could have translational implications for novel therapeutic outcomes.

AB - Fibroblast growth factor-21 (FGF21) beneficially affects carbohydrate and lipid metabolism. Previously, a sex-specific activation of Fgf21 expression was observed in humans and animals with metabolic diseases. It is unknown whether the sex differences in the Fgf21 expression are manifested in response to the natural physiological situations of fasting and refeeding. The aim of this work was to determine liver, White Adipose Tissue (WAT) and Brown Adipose Tissue (BAT) expression of genes related to FGF21 signaling in response to 24 h fasting, 6 h refeeding (after 24 h fasting) and Diet-Induced Obesity (DIO) in C57Bl mice of both sexes. Obesity was induced by the consumption of palatable food for 10 weeks. mRNA levels of peroxisome proliferator-activated receptor-a and -γ (Pparα, Pparγ), FGF21 (Fgf21), coactivator of FGF receptors (Klb) and transcriptional coactivator (Pgc-1α) were measured by RT-PCR. The study showed that the fasting-induced increases in hepatic Fgf21 gene expression and circulating FGF21 levels, as well as refeeding-induced increases in local WAT and BAT Fgf21 gene expression, were biased toward females. DIO-induced increase in circulating FGF21 levels, as well as in Fgf21 gene expression in the liver and BAT, were biased toward males. Considering that FGF21 is a novel metabolic regulator of energy homeostasis, sex differences in the responses to anabolic and catabolic stimulus could have translational implications for novel therapeutic outcomes.

KW - Diet-Induced Obesity

KW - Fasting

KW - Mice

KW - Refeeding

KW - Sex-Specific FGF21 Signaling

UR - http://www.scopus.com/inward/record.url?scp=85067402299&partnerID=8YFLogxK

U2 - 10.3844/ojbsci.2019.28.36

DO - 10.3844/ojbsci.2019.28.36

M3 - Article

AN - SCOPUS:85067402299

VL - 19

SP - 28

EP - 36

JO - OnLine Journal of Biological Sciences

JF - OnLine Journal of Biological Sciences

SN - 1608-4217

IS - 1

ER -